Wang Rui, Wang Yiqin, Tao Yiran, Hu Liqiang, Qiu Qi, Pu Qianlun, Yang Juqin, Wang Shisheng, Huang Yan, Chen Xiaoting, Zhu Ping, Yang Hao, Xia Qing, Du Dan
West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China.
Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
ACS Omega. 2023 Mar 21;8(13):12310-12326. doi: 10.1021/acsomega.3c00019. eCollection 2023 Apr 4.
The pathophysiological mechanisms of acute pancreatitis (AP) are complex and have remained a mystery to date, but metabolism is gradually recognized as an important driver of AP onset and development. We used a cerulein-induced AP mouse model to conduct liquid chromatography-mass spectrometry (LC-MS/MS)-based time-course proteomics and lipidomics in order to better understand the underlying metabolic alterations linked with AP. Results showed that a series of significant changes in proteins over time with a boost in expression were enriched in lipase activity, lipoprotein, and lipids absorption and transport regulation. Furthermore, 16 proteins associated with lipid metabolism and signaling pathways together with the whole lipid species changing profile led to the vital identification of changing law in glycerides, phosphoglycerides, and free fatty acids. In addition to lipid metabolism and regulation-associated proteins, several digestive enzymes and adaptive anti-trypsin, stress response, and energy metabolism-related proteins showed an increment in abundance. Notably, central carbon and branched chain amino acid metabolism were enhanced during 0-24 h from the first cerulein stimulation. Taken together, this integrated proteomics and lipidomics revealed a novel metabolic insight into metabolites transforming rules that might be relevant to their function and drug targets investigation. (Created with Biorender.com.).
急性胰腺炎（AP）的病理生理机制复杂，至今仍是个谜，但代谢逐渐被认为是AP发病和发展的重要驱动因素。我们使用雨蛙素诱导的AP小鼠模型进行基于液相色谱-质谱联用（LC-MS/MS）的时间进程蛋白质组学和脂质组学研究，以更好地了解与AP相关的潜在代谢改变。结果显示，随着时间推移，一系列蛋白质表达上调的显著变化富集于脂肪酶活性、脂蛋白以及脂质吸收和转运调节方面。此外，16种与脂质代谢和信号通路相关的蛋白质以及整个脂质种类的变化谱，使得甘油酯、磷酸甘油酯和游离脂肪酸的变化规律得以明确识别。除了与脂质代谢和调节相关的蛋白质外，几种消化酶以及适应性抗胰蛋白酶、应激反应和能量代谢相关蛋白质的丰度也有所增加。值得注意的是，从首次雨蛙素刺激开始的0至24小时内，中心碳代谢和支链氨基酸代谢增强。综上所述，这种整合的蛋白质组学和脂质组学揭示了对代谢物转化规律的新的代谢见解，这可能与其功能和药物靶点研究相关。（由Biorender.com创建。）
